1. Field of the Invention
The present invention belongs to the field of pharmaceutical chemistry, and provides a useful intermediate for the synthesis of nizatidine, an important and relatively new H.sub.2 -receptor antagonist, which is used primarily for the treatment of gastric ulcers.
2. State of the Art
The H.sub.2 receptor antagonists have been studied for some years, and a very extensive literature has been built up around them. The most prominent individual drugs are probably cimetidine, N-cyano-N'-methyl-N"-[2-([(5-methyl-1H-imidazol-4-yl)methyl]thio)ethyl]-gu anidine, and ranitidine, N-methyl-N'-2-(5-dimethylaminomethylfur-2-ylmethylthio)ethyl-2-nitro-1,1-e thenediamine. Cimetidine is taught by Durant et al., U.S. Pat. No. 3,950,333, and ranitidine is disclosed by Price et al., in U.S. Pat. No. 4,128,658.
Further disclosures from the voluminous H.sub.2 -receptor literature which are particularly pertinent to the present invention include U.S. Pat. No. 4,239,769, of Price et al., which discloses at columns 3 and 4 a synthesis process which proceeds through an S-methyl isothiourea intermediate. The objective of that synthesis, however, is a class of compounds wherein the heterocyclic ring is thiophene.
U.S. Pat. No. 3,950,333 also makes use of a number of S-methyl isothiourea intermediates, such as those of Examples 55, 64, 75, 121 and others.
British Pat. No. 2,067,987, of Crenshaw et al., shows as its Example 22E the compound which is the starting compound for the present invention, 4-(2-aminoethyl)thiomethyl-2-dimethylaminomethylthiazole.
U.S. Pat. No. 4,200,578, of Algieri et al., shows 2-nitro-1,1-ethenediamine compounds, having a relationship to the ultimate product of the present invention, but wherein the terminal nitrogen is substituted with an alkynyl group. Algieri's compounds have a thiazole ring, but the patent states a preference for attaching the "tail" ending in the ethenediamine group to the 2-position of the thiazole ring, rather than the 4-position.
Nizatidine, the ultimate product of the present invention, is disclosed in allowed U.S. application Ser. No. 319,155, of Pioch.